CN113402866A - 一种基于形状记忆调控药物释放的聚合物 - Google Patents

一种基于形状记忆调控药物释放的聚合物 Download PDF

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CN113402866A
CN113402866A CN202110770695.1A CN202110770695A CN113402866A CN 113402866 A CN113402866 A CN 113402866A CN 202110770695 A CN202110770695 A CN 202110770695A CN 113402866 A CN113402866 A CN 113402866A
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CN113402866B (zh
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宋晓峰
任亚君
魏君格
沈月石
刘磊
曲瑞
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Changchun University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • C—CHEMISTRY; METALLURGY
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    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
    • C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
    • C08F283/065—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals on to unsaturated polyethers, polyoxymethylenes or polyacetals
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    • C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2451/00—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers
    • C08J2451/08—Characterised by the use of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives of such polymers grafted on to macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds

Abstract

本发明涉及一种基于形状记忆调控药物释放的网络状聚合物。该网络状聚合物是以含有较多活性双键D4 vi为网络中心，引发醋酸乙烯酯（VAc）、丙烯酸（AA）和改性后的聚四氢呋喃（PTMG）聚合得到的网络，其中P(VAc‑AA)增容和亲水段、PTMG软段。该网络状聚合物制备过程简单，不但较低温度下（60℃）即可实现融化与重结晶，而且具有超强吸水性，能够赋予PLA水诱导形状记忆效应，且形状记忆恢复时间短，恢复效果好。同时，形状恢复过程中（触水或热）网络状聚合物链运动，打开分子间通道，可以加快药物释放速度

Description

一种基于形状记忆调控药物释放的聚合物
技术领域
本发明涉及高分子形状记忆与药物释放领域，特别涉及一种以D4 vi为网络状中心，网络链上含有P(VAc-AA)增容和亲水段、PTMG软段的网络状聚合物，该聚合物与PLA共混复合材料具备水和热诱导形状记忆功能，并且可以控制药物释放。
背景技术
具有一定形状的固体材料，在某种外界条件刺激下发生塑性形变，在经过特定环境刺激，材料又完全恢复到变形前形状的现象被称为形状记忆效应。根据实现记忆功能的环境条件不同，可分为感温型、感水型、感光型和感酸碱型等多种记忆材料，目前应用研究最多的是热致形状记忆和水诱导形状记忆高分子材料。
PLA作为用途广泛的生物可降解聚酯，常用作组织工程支架作为药物传送材料。将形状记忆能力与其结合，形状记忆是聚合物分子链重排的过程。我们想通过在PLA中添加合成单体，使用此类单体作为起始材料，使PLA具备形状记忆功能，近而获得结合形状记忆能力、生物降解性和可控药物释放的多功能系统。
发明内容
为了实现上述目的，本发明提供了一种基于形状记忆调控药物释放的聚合物，恢复条件简单，恢复时间短，控制药物释放速度，同时可以有效提高聚乳酸的韧性与亲水性。
本发明的技术方案：合成一种以D4 vi为中心，PTMG（T g = -76℃）为软段，P(VAc-AA)增容和亲水段的网络状聚合物PMVS柔性嵌段，共混PLA（T g = 62℃）。因为合成的聚合物具有良好的吸水性，并且与PLA的T g 相差较多，从而通过在水环境中吸水以及热辅助实现PLA的形状记忆，在形状恢复过程中网络状聚合物链运动，从而加速药物释放。
所述一种基于形状记忆调控药物释放的聚合物，其分子网络状中心为D4 vi结构如下：
Figure 716309DEST_PATH_IMAGE001
。
所述一种基于形状记忆调控药物释放的聚合物，其分子网络链上含有P(VAc-AA)增容和亲水段的结构如下：
Figure 911798DEST_PATH_IMAGE002
，m为大于1的整数。
所述一种基于形状记忆调控药物释放的聚合物，其分子网络链上PTMG软段的结构如下：
Figure 872801DEST_PATH_IMAGE003
，n为大于1的整数。
附图说明
图1为网络状聚合物的核磁共振氢谱图。
如图1所示， 核磁谱图中，a (0～0.4ppm)之间为D4 vi中-Si-CH3氢的化学位移，b(1.56ppm)和f (3.33ppm)为PTMG中-CH2-氢的化学位移，c (1.78ppm)和d (1.95ppm)分别为VAc中-CH2-和-CH3氢的化学位移，e (2.22ppm)和g (3.61ppm)为AGE中-CH2-氢的化学位移，i(12.24ppm)左右羧基上氢的化学位移出现说明AA聚合。采用1H-NMR表征的结果说明一种以D4 vi为中心，PTMG为软段，P(VAc-AA)增容和亲水段的网络状聚合物已经合成。
图2为本发明制备的网络状聚合物与PLA共混薄膜形状记忆的过程。A为60℃热恢复，B为水中恢复（a-初始形状，b-临时形状，c-恢复后形状）。
图3为本发明制备的网络状聚合物与PLA共混薄膜在不同温度下药物释放情况（A为25℃释放，B为37℃释放）。
具体实施方式
下面通过实施例对本发明进行具体描述。
实施例1：
称重适量PTMG和烯丙基缩水甘油醚（AGE）放置于配有磁力搅拌棒的安瓿瓶中，通氮气，一定量四氢呋喃溶剂65℃下搅拌45min后升温到125℃，滴加浓硫酸（四氢呋喃稀释）催化剂反应5h，去离子水回流1h终止反应。反应后混合物分层，上层溶液减压蒸馏除去未反应的单体，产物40℃真空干燥12h。将上诉所得产物与一定量VAc置于三口烧瓶中，通氮气，四氢呋喃做溶剂，偶氮二异丁氰做催化剂，温度控制65℃，通过滴定漏斗滴加AA，反应5h，获得网络状产物沉降并干燥。
将PLA、网络状聚合物（其中含10wt%水杨酸）按质量比7:3分别溶于三氯甲烷和四氢呋喃溶剂当中，然后再混合均匀，其中PLA和网络状聚合物的浓度为29wt%，室温搅拌过夜。将搅拌过夜的溶液倒到玻璃板上，让溶液在玻璃板上自由流延。在常温（20℃左右）和常压自然挥发2h，待膜在空气中固化后，随后将样条加工成型，2天后形状固定，然后25℃抽真空干燥备用。
将加工成型的薄膜，放置于60℃环境中一段时间，随后将其固定临时形状。分别放置于60℃环境和水中，迅速恢复初始形状，说明网络状聚合物可以赋予PLA水和热诱导形状记忆功能。
将PLA/水杨酸和PLA/网络状产物/水杨酸混合膜20mg分别放置于25℃和37℃的20mlPH=7.4的磷酸盐缓冲溶液中，测试不同时间水杨酸释放量。

Claims (1)

1.一种基于形状记忆调控药物释放的聚合物，其特征在于：网络状中心为D4 vi，网络链上含有P(VAc-AA)增容和亲水段、PTMG软段
其分子结构如下：
Figure 437477DEST_PATH_IMAGE001
一种基于形状记忆调控药物释放的聚合物，其分子网络状中心为D4 vi结构如下：
Figure 259939DEST_PATH_IMAGE002
一种基于形状记忆调控药物释放的聚合物，其分子网络链上含有P(VAc-AA)增容和亲水段的结构如下：
Figure 589289DEST_PATH_IMAGE003
，m为大于1的整数
一种基于形状记忆调控药物释放的聚合物，其分子网络链上PTMG软段的结构如下：
Figure 788189DEST_PATH_IMAGE004
，n为大于1的整数。
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